Effect of MDMA-Induced Axotomy on the Dorsal Raphe Forebrain Tract in Rats: An In Vivo Manganese-Enhanced Magnetic Resonance Imaging Study.
Chuang-Hsin Chiu, Tiing-Yee Siow, Shao-Ju Weng, Yi-Hua Hsu, Yuahn-Sieh Huang, Kang-Wei Chang, Cheng-Yi Cheng, Kuo-Hsing Ma
PLoS ONE June 10, 2016 DOI: 10.1371/journal.pone.0138431 via DOAJ
Summary
AI-generated from the abstractMDMA (Ecstasy) damages the fine serotonergic axons that connect the raphe nucleus to the striatum, a disruption previously inferred but not directly observed in living animals. Using manganese-enhanced magnetic resonance imaging (MEMRI) in rats, the study tracked manganese ions injected into the raphe nucleus as they traveled along neural pathways. Eight days after repeated MDMA injections (5 mg/kg daily for six days), MEMRI showed reduced signal enhancement in the medial forebrain bundle and striatum, indicating disrupted axonal transport. Immunohistological staining confirmed a loss of serotonin transporters. The findings provide direct in vivo evidence that MDMA causes axonal damage in these serotonergic projections.
Study at a glance
| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | MDMA |
| Dose | 5 mg/kg |
| Duration | Six daily injections, imaging over 38 hours starting eight days after the last injection |
| Citations | 9 |
| Key finding | MDMA disrupts serotonergic raphe-striatal projections in rats, as visualized in vivo by MEMRI. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA), also known as "Ecstasy", is a common recreational drug of abuse. Several previous studies have attributed the central serotonergic neurotoxicity of MDMA to distal axotomy, since only fine serotonergic axons ascending from the raphe nucleus are lost without apparent damage to their cell bodies. However, this axotomy has never been visualized directly in vivo. The present study examined the axonal integrity of the efferent projections from the midbrain raphe nucleus after MDMA exposure using in vivo manganese-enhanced magnetic resonance imaging (MEMRI). Rats were injected subcutaneously six times with MDMA (5 mg/kg) or saline once daily. Eight days after the last injection, manganese ions (Mn2+) were injected stereotactically into the raphe nucleus, and a series of MEMRI images was acquired over a period of 38 h to monitor the evolution of Mn2+-induced signal enhancement across the ventral tegmental area, the medial forebrain bundle (MFB), and the striatum. The MDMA-induced loss of serotonin transporters was clearly evidenced by immunohistological staining consistent with the Mn2+-induced signal enhancement observed across the MFB and striatum. MEMRI successfully revealed the disruption of the serotonergic raphe-striatal projections and the variable effect of MDMA on the kinetics of Mn2+ accumulation in the MFB and striatum.